The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference.
Conventionally antagonists of alpha-2-adrenoceptors, such as yohimbine, have been found to be anxiogenic (1). Three subtypes, namely alpha-2A-, alpha-2B- and alpha-2C-adrenoceptors have been discovered in human. A fourth subtype, an alpha-2D-adrenoceptor, is known in rat and bovine. According to literature, most of the known alpha-2-adrenoceptor antagonists are not specific to any certain subtype (alpha-2A to alpha-2D). As examples of such nonspecific alpha-2-adrenoceptor antagonists can be mentioned rauwolscine, yohimbine, idazoxan, atipamezole and RX821002 (reference 6, Marjamaki et al.).
However, because alpha-2-adrenoceptor subtypes have a discrete pattern of distribution in the brain (2) so that the alpha-2C-adrenoceptor appears to be distributed along the limbic system (a complex brain area related to affections and other mental functions), we made a hypothesis that a behavioural response of a subtype C selective alpha-2-adrenoceptor antagonist would be different from that of a non-subtype selective.